Diisopropylethylamine → tert-butyl-N-[1-oxo-1-[[1-[2-(1,3-thiazol-4-yl)ethynyl]isoquinolin-3-yl]-amino]propan-2-yl]carbamate

HRID 535435Notes

Reaction equation

HRID 535435 reaction equation
[C:1]([O:5][C:6](=[O:25])[NH:7][CH:8]([CH3:24])[C:9]([NH:11][C:12]1[N:13]=[C:14]([C:22]#[CH:23])[C:15]2[C:20]([CH:21]=1)=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:10])([CH3:4])([CH3:3])[CH3:2].Br[C:27]1[N:28]=[CH:29][S:30][CH:31]=1.CCN(C(C)C)C(C)C>CN1C(=O)CCC1.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:1]([O:5][C:6](=[O:25])[NH:7][CH:8]([CH3:24])[C:9](=[O:10])[NH:11][C:12]1[N:13]=[C:14]([C:22]#[C:23][C:27]2[N:28]=[CH:29][S:30][CH:31]=2)[C:15]2[C:20]([CH:21]=1)=[CH:19][CH:18]=[CH:17][CH:16]=2)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 27632184-BromothiazoleHCID 86694379tert-butyl-N-[1-[(1-ethynylisoquinolin-3-yl)amino]-1-oxopropan-2-yl]-carbamate

Product 1

HCID 86694426tert-butyl-N-[1-oxo-1-[[1-[2-(1,3-thiazol-4-yl)ethynyl]isoquinolin-3-yl]-amino]propan-2-yl]carbamate

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A mixture of tert-butyl-N-[1-[(1-ethynylisoquinolin-3-yl)amino]-1-oxopropan-2-yl]-carbamate D4a (50 mg, 0.15 mmol), 4-bromo-1,3-thiazole (24 mg, 0.15 mmol), copper(I) iodide (3 mg, 0.02 mmol), Dichlorobis(triphenylphosphine)palladium(II) (10 mg, 0.01 mmol) and DIPEA (75 μl, 0.44 mmol) is stirred under argon atmosphere in NMP (1 ml) for 2 h at 80° C. The mixture is concentrated in vacuo and the product purified by RP HPLC. Yield: 12 mg (19%). HPLC-MS: M+H=423; tR=1.84 min (*Method—4).

Workup

  1. concentrationThe mixture is concentrated in vacuo
  2. customthe product purified by RP HPLC

Sources & evidence

ORD record
ord-5aa4845ca8c44839a4322f5c87e36cdb
Source dataset
uspto-grants-2014_10
Patent number
US08859541B2

Reaction notes

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